Hans Ole Hein

Type of Alcohol Consumed and Mortality from All Causes, Coronary Heart Disease, and Cancer

Several population studies from different countries have shown a J-shaped relation between intake of alcohol and mortality from all causes (1-6). Studies comparing different countries have found a strong inverse relation between incidence rates of coronary heart disease and wine consumption but a weak or nonexistent relation for consumption of beer or spirits (7-9). The findings that different types of alcoholic beverages have different effects on mortality are indirectly supported by several clinical and experimental studies (10-12). In contrast, prospective studies have shown that beer (13), spirits (14), and wine (15) may have protective effects. However, most of these investigations were based on populations with one predominant type of alcohol consumption; this precluded valid comparison of the effects of the three different types of alcohol. We sought to analyze the effect of intake of different types of alcohol on mortality from all causes, coronary heart disease, and cancer in several large Danish cohort studies. Methods The Copenhagen Centre for Prospective Population Studies is based on three study samples: that of the Copenhagen City Heart Study; that of the Copenhagen County Centre of Preventive Medicine (the former Glostrup Population Studies), which includes six cohorts; and that of the Copenhagen Male Study (16-18). The study samples of the Copenhagen City Heart Study, initiated in 1976, and the Copenhagen County Centre of Preventive Medicine, initiated in 1964, were randomly selected within age strata from the populations residing in defined areas in greater Copenhagen. For the Copenhagen Male Study, initiated in 1971, employees of 14 large companies in Copenhagen were invited to participate. The mean participation rate in all studies was 80% (range, 69% to 88%). The combined study sample comprises 13 064 men and 11 459 women for whom information on alcohol intake and lifestyle-related variables, described below, was complete. Alcohol Intake Participants of the Copenhagen City Heart Study and the studies in the Copenhagen County Centre of Preventive Medicine were asked about their current average weekly intake of beer, wine, and spirits. In the Copenhagen Male Study, participants were asked about their average daily intake of beer, wine, and spirits on weekdays (Monday through Thursday) and weekends (Friday through Sunday); these reports were combined to estimate weekly alcohol consumption. Persons in our study who did not drink alcohol because they were receiving disulfiram or other medication were excluded from the analysis. One bottle of beer contains 11.6 g of alcohol, and 12 g is an approximate average for one serving of wine or spirits. We grouped participants into five categories on the basis of total intake of alcohol: less than 1 drink/wk (nondrinkers), 1 to 7 drinks/wk, 8 to 21 drinks/wk, 22 to 35 drinks/wk, and more than 35 drinks/wk. Intake of beer, wine, and spirits was categorized similarly; however, because of the frequency of end point data, more than 21 drinks/wk is the highest intake category for the individual types of beverages. Smoking Status Participants reported whether they were never-smokers, former smokers, or current smokers. Current smokers reported grams of tobacco smoked per day in the form of cigarettes (1 g/d), small cigars (3 g/d), cigars (5 g/d), and pipe tobacco (50 g/package). Five groups were defined: never-smokers, former smokers, smokers of 1 to 14 g of tobacco daily, smokers of 15 to 24 g of tobacco daily, and smokers of more than 24 g of tobacco daily. Education Participants reported the number of years that they attended school. Three groups were defined: fewer than 8 years, 8 to 11 years, and 12 or more years of school education. Physical Activity Participants reported whether they were physically active during leisure time. Four groups were defined: sedentary (<2 h/wk), light activity (2 to 4 h/wk), moderate activity (>4 h/wk, noncompetitive) and heavy activity (>4 h/wk, competitive). Body Mass Index Body weight and height were measured while the participant was wearing light clothes and no shoes. Body mass index was calculated as weight in kg divided by height in meters squared. Five categories of body mass index were defined: less than 20.0 kg/m2, 20.0 to 24.9 kg/m2, 25.0 to 29.9 kg/m2, 30.0 to 34.9 kg/m2, and 35.0 kg/m2 or more. Changes in Lifestyle-Related Variables When participants were re-examined during follow-up, the newly obtained values for alcohol intake, smoking status, physical activity, and body mass index were used to replace the old values in the statistical analyses. Observation time and vital status were included in the modeling accordingly. Follow-up Participants were followed from date of entry into the study to date of death, loss to follow-up, emigration, or end of follow-up, whichever came first. The vital status of populations was followed by using each participants unique identification number in the national Central Person Register until 9 January 1995. Fewer than 1% of the participants were lost to follow-up. Causes of death were obtained from the National Board of Health and were defined by using codes from International Classifications of Diseases, Eighth Revision (codes 410.0 to 414.0 for coronary heart disease and codes 140.0 to 209.0 for cancer). According to a previous study, the reported diagnoses for these grouped codes have proven to be sufficiently valid (20). Statistical Analysis We performed Poisson regression (21) by using SAS/STAT software (22) to estimate the effect of alcohol intake on the risk for death. These models generate estimates of relative risk that are adjusted for confounders. Each model included the following potential confounders as categorical variables: age, cohort study, sex, education, body mass index, physical activity, and smoking status. Owing to collinearity, it was impossible to include both the amount by type of beverage (beer, wine, or spirits) consumed and total alcohol intake in the same regression. We therefore estimated the influence of alcohol according to number of drinks consumed per week [0, 1 to 7, 8 to 21, 22 to 35,>35] in three regressions: 1) total alcohol consumption in drinks per week, without considering beverage type; 2) alcohol consumption in drinks of each beverage per week, without considering the total intake; and 3) percentage of total alcohol intake consumed as wine (0%, 1% to 30%,>30%). Effects that were insignificant according to the likelihood ratio test (5% level) were removed by backward elimination. A term indicating interaction between total alcohol intake and percentage alcohol consumed as beer, wine, or spirits was included in the analyses to assess whether the effects of beer, wine, and spirits differed at different levels of total alcohol intake; no such effects were identified, as judged from the fit of the model. Likewise, no interaction was found between sex and intake of different types of beverage in terms of mortality. Results A total of 4275 women and 1635 men drank less than 1 drink per week; 64 women and 1032 men drank 35 or more drinks per week. Of 13 613 participants who drank alcohol, 12 846 (69%) included wine in their intake (Table 1). During 257 859 person-years of follow-up, 4833 participants died; of these, 1075 died of coronary heart disease and 1552 died of cancer. Table 1. Baseline Characteristics of the Study Participants Baseline Characteristics Compared with participants who drank alcohol but no wine, those for whom wine made up more than 30% of their total alcohol intake were more likely to be women and have a higher educational level but were less likely to be smokers (Table 1). Participants for whom wine made up more than 30% of their alcohol intake were similar to those who drank no alcohol in terms of smoking habits, body mass index, and physical activity. Across categories of total alcohol intake, mean alcohol intake within the different categories of wine drinking was similar; for example, among participants who drank 8 to 21 drinks/wk, those who drank no wine, those who drank 1% to 30% wine, and those who drank more than 30% wine had a mean alcohol intake of 13.3, 13.7, and 12.8 drinks/wk, respectively. However, among light drinkers (1 to 7 drinks/wk), those who drank 1% to 30% of their alcohol as wine had a slightly higher mean intake than did those who avoided wine and those who drank more than 30% of their alcohol intake as wine. Thus, assessment of the effects of wine intake may not be subject to residual confounding by total alcohol intake when controlled for as specified. Total Alcohol Intake and Mortality We found J-shaped relations between total alcohol intake and all-cause mortality in the three substudies. Pooled analyses also revealed J-shaped relations (Table 2). When nondrinkers were used as the reference group (relative risk, 1.00), intake of 1 to 7 drinks per week carried a relative risk of 0.82 (95% CI, 0.76 to 0.88) and intake of more than 35 drinks per week carried a relative risk of 1.10 (CI, 0.95 to 1.26). Alcohol intake was negatively related to death from coronary heart disease and positively related to death from cancer (Table 2). Table 2. Relative Risk for Death with Regard to Total Alcohol Intake and Intake of Beer, Wine, and Spirits Intake of Beer, Wine, and Spirits and Mortality Light to moderate intake of beer or spirits had a small effect on death from all causes (Table 2). This finding contrasted with the effect of wine intake on mortality: Participants who drank 8 to 21 glasses of wine per week had a relative risk for death from all causes of 0.76 (CI, 0.67 to 0.86). Intake of fewer than 22 drinks of beer, wine, and spirits per week all carried lower risk for death from coronary heart disease; the reduction in risk was of the same magnitude for beer and wine drinking but was smaller and not statistically significant for spirits drinking. Furthermore, light to moderate drinkers of wine had

Smoking and risk of myocardial infarction in women and men : longitudinal population study

Abstract Objective: To compare risk of myocardial infarction associated with smoking in men and women, taking into consideration differences in smoking behaviour and a number of potential confounding variables. Design: Prospective cohort study with follow up of myocardial infarction. Setting: Pooled data from three population studies conducted in Copenhagen. Subjects: 11 472 women and 13 191 men followed for a mean of 12.3 years. Main outcome measures: First admission to hospital or death caused by myocardial infarction. Results: 1251 men and 512 women had a myocardial infarction during follow up. Compared with non-smokers, female current smokers had a relative risk of myocardial infarction of 2.24 (range 1.85-2.71) and male smokers 1.43 (1.26-1.62); ratio 1.57 (1.25-1.97). Relative risk of myocardial infarction increased with tobacco consumption in both men and women and was higher in inhalers than in non-inhalers. The risks associated with smoking, measured by both current and accumulated tobacco exposure, were consistently higher in women than in men and did not depend on age. This sex difference was not affected by adjustment for arterial blood pressure, total and high density lipoprotein cholesterol concentrations, triglyceride concentrations, diabetes, body mass index, height, alcohol intake, physical activity, and level of education. Conclusion: Women may be more sensitive than men to some of the harmful effects of smoking. Interactions between components of smoke and hormonal factors that may be involved in development of ischaemic heart disease should be examined further.

Serum selenium concentration and risk of ischaemic heart disease in a prospective cohort study of 3000 males.

Whether an association, causative or not, exists between the level of serum selenium and the risk of ischaemic heart disease (IHD) remains unsettled. We investigated the issue in a cohort of 3387 males aged 53-74 years (mean 63). Based on information about health status, life-style and socioeconomic factors given in a prefilled comprehensive questionnaire, the men were interviewed and the information validated. Following the interview, they underwent a clinical examination and had a venous blood sample drawn for the determination of a number of biochemical characteristics. Three hundred and forty-six men were excluded due to prevalent cardiovascular disease, including stroke. During the next three years (1986-1989) 107 men (approximately 3%) suffered an IHD event; 25 events were fatal. Compared to others, men with serum selenium levels less than or equal to 1 mumol/l, approximately the lowest tertile, had a 70% increased risk of IHD, relative risk (RR) with 95% confidence limits was 1.70 (1.14-2.53). After multivariate adjustment for cholesterol, social class, smoking and age, RR was 1.55 (1.00-2.39). Serum selenium level was significantly (P less than 0.05), but not strongly, correlated with a number of IHD risk factors: serum cotinine, tobacco smoking, social class, alcohol consumption, total cholesterol, hypertension, age and physical inactivity. Body mass index, HDL-cholesterol and triglycerides were not significantly associated with serum selenium. We conclude that middle-aged and elderly Danish men with serum selenium less than or equal to 1 mumol/l had a significantly increased risk of ischaemic heart disease. This association was not explained by the interrelationship of serum selenium and major cardiovascular risk factors.

Alcohol consumption, serum low density lipoprotein cholesterol concentration, and risk of ischaemic heart disease: six year follow up in the Copenhagen male study.

Abstract Objectives: To investigate the interplay between use of alcohol, concentration of low density lipoprotein cholesterol, and risk of ischaemic heart disease. Design: Prospective study with controlling for several relevant confounders, including concentrations of other lipid fractions. Setting: Copenhagen male study, Denmark. Subjects: 2826 men aged 53-74 years without overt ischaemic heart disease. Main outcome measure: Incidence of ischaemic heart disease during a six year follow up period. Results: 172 men (6.1%) had a first ischaemic heart disease event. There was an overall inverse association between alcohol intake and risk of ischaemic heart disease. The association was highly dependent on concentration of low density lipoprotein cholesterol. In men with a high concentration (>/=5.25 mmol/l) cumulative incidence rates of ischaemic heart disease were 16.4% for abstainers, 8.7% for those who drank 1-21 beverages a week, and 4.4% for those who drank 22 or more beverages a week. With abstainers as reference and after adjustment for confounders, corresponding relative risks (95% confidence interval) were 0.4 (0.2 to 1.0; P<0.05) and 0.2 (0.1 to 0.8; P<0.01). In men with a concentration <3.63 mmol/l use of alcohol was not associated with risk. The attributable risk (95% confidence interval) of ischaemic heart disease among men with concentrations >/=3.63 mmol/l who abstained from drinking alcohol was 43% (10% to 64%). Conclusions: In middle aged and elderly men the inverse association between alcohol consumption and risk of ischaemic heart disease is highly dependent on the concentration of low density lipoprotein cholesterol. These results support the suggestion that use of alcohol may in part explain the French paradox. Key messages Key messages The low risk of ischaemic heart disease in men with a low concentration of serum low density lipoprotein cholesterol was not modified by use of alcohol The risk of ischaemic heart disease in men with a high concentration of serum low density lipoprotein cholesterol was strongly modified by use of alcohol: those who did not drink alcohol had five times the risk of ischaemic heart disease compared with those who consumed three alcoholic beverages or more a day The results support the hypothesis that the apparent discrepancy between a low risk of ischaemic heart disease and a high intake of fat, a phenomenon known as the French paradox, may partly be explained by consumption of alcohol In studies of the use of alcohol and risk of ischaemic heart disease, serum low density lipoprotein cholesterol should be regarded as a potentially strong effect modifier not as a potential confounder

Physical activity in leisure-time and risk of cancer: 14-year follow-up of 28 000 Danish men and women.

Aim: The preventive effect of physical activity on risk of cancer in general remains controversial. This study aimed at assessment of the associations between leisure- time physical activity and incidence of cancer in the general population of adult men and women. Methods: 13,216 women and 18,718 men aged 20—93 years selected from the general population participated in a health examination including a questionnaire with information on physical activity, smoking, alcohol intake, postmenopausal hormones, and socioeconomic status. Incident cases of cancers where recorded during a follow-up period of 14 years. The six most frequent cancer cases in both sexes were included in this analysis. Results: A highly significant inverse association was seen between vigorous physical activity in leisure time and cancer of the ovary, adjusted rate ratio being 0.33 (95% CI 0.16—0.67; p=0.001) for the most physical active women. In men there was a highly significant increase for non-melanoma skin cancer, with adjusted rate ratio of 1.72 (95% CI 1.23—2.40; p=0.001), for the most active men and vigorous activity was associated with a non-significant lower risk of colon cancer, the adjusted rate ratio being 0.72 (95% CI 0.47—1.11; p=0.06). Conclusion: Generally, there were no, or only weakly, inverse associations between physical activity in leisure time and incidence of cancer, except for cancer of the ovary.

Shift work, social class, and ischaemic heart disease in middle aged and elderly men; a 22 year follow up in the Copenhagen Male Study.

OBJECTIVES: Shift work has been associated with an increased risk of ischaemic heart disease (IHD). Most published studies have had potential problems with confounding by social class. This study explores shift work as a risk factor for IHD after controlling for social class. METHODS: The Copenhagen male study is a prospective cohort study established in 1970-1 comprising 5249 men aged 40-59. Information obtained included working time, social class, and risk factors for IHD. A second baseline was obtained in 1985-6. The cohort was followed up for 22 years through hospital discharge registers for IHD, and cause of death was recovered from death certificates. RESULTS: One fifth of the cohort was shift working at entry with a significantly larger proportion of shift workers in lower social classes. Risk of IHD and all cause mortality over 22 years, adjusted for age only, for age and social class, and finally for age, social class, smoking, fitness, height, weight, and sleep disturbances, did not differ between shift and day workers. The relative risk of IHD, adjusted for age and social class was 1.0 (95% confidence interval (95% CI) 0.9-1.2). Men being shift workers in both 1971 and 1985 had the same risk as ex-shift workers in an 8 years follow up from the 1985-6 baseline. CONCLUSIONS: The present study questions shift work as an independent risk factor for IHD. The results of the study emphasise the importance of controlling adequately for the interplay of shift work and social class.

Changes in alcohol intake and mortality: a longitudinal population-based study.

Background: Using alcohol intake at one point in time, numerous studies have shown a J- or U-shaped relation with all-cause mortality. Mortality is lowest among the light to moderate drinkers, with the risk of dying from coronary heart disease higher among nondrinkers and the risk of dying from cancer higher among heavy drinkers. We studied whether changes in individual alcohol intake result in corresponding changes in mortality. Methods: In a longitudinal study of 6644 men and 8010 women, age 25 to 98 years, who had attended at least 2 health surveys with a 5-year interval between them, we addressed the risk of death after combinations of changes in alcohol intake. Results: Mortality after changes in alcohol intake was consistent with the mortality observed among those who reported stable drinking. Stable drinkers showed a U-shaped all-cause mortality, with relative risks of 1.29 (95% confidence interval [CI] = 1.13–1.48) for nondrinkers (<1 drink per week) and 1.32 (1.15–1.53) for heavy drinkers (>13 drinks per week) compared with light drinkers (1 to 6 drinks per week). For coronary heart disease mortality, stable nondrinkers had a relative risk of 1.32 (0.97–1.79) compared with stable light drinkers and those who had reduced their drinking from light to none increased their risk (1.40; 1.00–1.95), and those who had increased from nondrinking to light drinking reduced their relative risk ratio (0.71; 0.44–1.14). Cancer mortality was increased in all groups of heavy drinkers. Conclusion: Persons with stable patterns of light and moderate alcohol intake had the lowest all-cause mortality. Individual changes in alcohol intake were followed by corresponding changes in mortality.

High Triglycerides and Low HDL Cholesterol and Blood Pressure and Risk of Ischemic Heart Disease

Treatment of high blood pressure (BP) has not produced the expected reduction in risk of ischemic heart disease (IHD). Subjects with high BP often have the metabolic syndrome X, an aggregation of abnormalities in glucose and lipid metabolism. We tested the hypothesis that the BP level would be less predictive of risk of IHD in those with high triglycerides (TG) and low HDL cholesterol (HDL-C), the characteristic dyslipidemia in the metabolic syndrome than in those without. Baseline measurements of fasting lipids, systolic BP (SBP), diastolic BP (DBP), and other risk factors were obtained in 2906 men, age 53 to 74 years, free of overt cardiovascular disease. High TG/low HDL-C was defined as TG >1.59 mmol/L and HDL-C <1.18 mmol/L. Within an 8-year period, 229 men developed IHD. In men with high TG/low HDL-C, the incidence of IHD according to SBP (<120, 120 to 140, >140 mm Hg) was 12.5%, 12.9%, and 10.0% (P=NS), respectively, and according to DBP, the incidence of IHD was (<75, 75 to 90, >90 mm Hg) 13.7%, 10.6%, and 13.7% (P=NS), respectively. The corresponding figures for other men were 5.2%, 8. 0%, and 9.7% for SBP (P<0.001), and 6.1%, 7.5%, and 9.9% for DBP (P<0.03). In conclusion, the BP level did not predict the risk of IHD in those with high TG/low HDL-C. This finding may explain the reason lowering BP has not produced the expected reduction in IHD.

Alcohol consumption, Lewis phenotypes, and risk of ischaemic heart disease

We have previously found an increased risk of ischaemic heart disease (IHD) in men with the Lewis phenotype Le(a-b-) and suggested that the Lewis blood group has a close genetic relation with insulin resistance. We have investigated whether any conventional risk factors explain the increased risk in Le(a-b-) men. 3383 men aged 53-75 years were examined in 1985-86, and morbidity and mortality during the next 4 years were recorded. At baseline, we excluded 343 men with a history of myocardial infarction, angina pectoris, intermittent claudication, or stroke. The potential risk factors examined were alcohol consumption, physical activity, tobacco smoking, serum cotinine, serum lipids, body-mass index, blood pressure, prevalence of hypertension and non-insulin-dependent diabetes mellitus, and social class. In 280 (9.6%) men with Le(a-b-), alcohol was the only risk factor significantly associated with risk of IHD. There was a significantly inverse dose-effect relation between alcohol consumption and risk; trend tests, with adjustment for age, were significant for fatal IHD (p = 0.02), all IHD (p = 0.03), and all causes of death (p = 0.02). In 2649 (90.4%) men with other phenotypes, there was a limited negative association with alcohol consumption. In Le(a-b-) men, a group genetically at high risk of IHD, alcohol consumption seems to be especially protective. We suggest that alcohol consumption may modify insulin resistance in Le(a-b-) men.

Coffee consumption and risk of ischaemic heart disease — a settled issue?

Abstract. Objective. Based on a meta‐analysis, it was recently stated that there is no association between coffee consumption and the risk of coronary heart disease. Why then, have studies on the issue shown quite variable results?